A method of screening highly common neoantigens with immunogenicity in colorectal cancer based on public somatic mutation library

Qin Lili, Li Yijian, Liang Zhaorui, Dai Lei, Li Wenhui, Chen Chao, Huang Yaling, Zhang Le, Liu Songming, Qiu Si, Ge Yuping, Peng Wenting, Lin Xinxin, Zhang Xiuqing, Dong Xuan, Li Bo

doi:10.16288/j.yczz.20-032

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Hereditas(Beijing) >

2020 , Vol. 42 >Issue 6: 599 - 612

DOI: https://doi.org/10.16288/j.yczz.20-032

Technique and Method

A method of screening highly common neoantigens with immunogenicity in colorectal cancer based on public somatic mutation library

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^1. BGI-Shenzhen, Shenzhen 518083, China
^2. College of Basic Medicine, Dali University, Dali 671000, China
^3. BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China
^4. BGI-GenoImmune, BGI-Shenzhen, Wuhan 430079, China

Received date: 2020-04-10

Revised date: 2020-05-15

Online published: 2020-05-19

Supported by

Supported by the National Natural Science Foundation of China No(81702826);Science, Technology and Innovation Commission of Shenzhen Municipality Nos(JCYJ20170303151334808);Science, Technology and Innovation Commission of Shenzhen Municipality Nos(JCYJ20170817150015170)

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Abstract

Colorectal cancer (CRC) is a malignant cancer with high incidence and mortality in the world. Immunotherapy targeting neoantigens can induce durable tumor regression in cancer patients, but is almost limited to personalized precision therapy, due to the individual differences of unique neoantigens. With the discovery of many common oncogenic mutations, and such mutation-associated neoantigens could cover more patients, and hence are valuable in clinical field. However, whether the common neoantigens can be identified in CRC is unknown. Combining the somatic mutations data from 321 CRC patients with a filter standard and 7 predicted algorithms, we screened and obtained 25 HLA-A*1101-restricted common neoantigens with a high binding affinity (IC₅₀<50 nmol/L) and presentation score (>0.90). Besides the positive epitope KRAS_G12V_8-16, 11 out of 25 common neoantigens specifically induced in vitro pre- stimulated cytotoxic lymphocyte (CTL) to secrete interferon gamma (IFN-γ). Moreover, combining cell-sorting technology and single-cell RNA sequencing, the immune repertoire profiles of C1orf170_S418G_413-421 and KRAS_G12V_8-16-specific CTL were analyzed and validated. Their related T-cell receptor engineered T cell (TCR-T) cells could also recognize the neoantigens and secrete IFN-γ. Hence, we have established a method to screen for common neoantigens with immunogenicity in CRC based on the public somatic mutation library. It can provide essential peptide and TCR information for immunotherapies, such as peptides, dendritic cells (DC) vaccines, TCR-like antibodies, TCR-T, etc., for the CRC and other cancers, which has practical application value in the clinics.

Key words： colorectal cancer; common; neoantigen; presentation

Cite this article

Qin Lili, Li Yijian, Liang Zhaorui, Dai Lei, Li Wenhui, Chen Chao, Huang Yaling, Zhang Le, Liu Songming, Qiu Si, Ge Yuping, Peng Wenting, Lin Xinxin, Zhang Xiuqing, Dong Xuan, Li Bo . A method of screening highly common neoantigens with immunogenicity in colorectal cancer based on public somatic mutation library[J]. Hereditas(Beijing), 2020 , 42(6) : 599 -612 . DOI: 10.16288/j.yczz.20-032

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